RT @AshAlizadeh: @majorajay For our friends and our colleagues, especially those in community oncology, if you had the proverbial gun to yo….

RT @everettmoding: Our study integrating ctDNA & radiomics to predict outcomes in NSCLC treated with CRT is online at @CD_AACR! A great col….

RT @Aiims1742: In @Nature from @StanfordMed by @max_diehn & @AshAlizadeh .An ultrasensitive method for detection of cell-free RNA. https://t….

We are extremely grateful for the patients & their families for participating in our study. We also greatly appreciate the support of @NIH @NCI @SU2C @Ludwig_Cancer, TRDRP, Troper/Wojcicki Foundations & others, without which this work would not have been possible. 15/15.

In sum, we describe development of a sensitive liquid biopsy method for #cfRNA analysis that has wide ranging potential applications in both cancer and benign disease. We hope our work will help to advance precision medicine and lead to improved treatments for patients. 14/15.

Finally, we profiled #cfRNA following COVID-19 mRNA vaccination. Vaccine RNA and host signatures of immune activation were both detectable in plasma, highlighting the potential of cfRNA as a pharmacokinetic and pharmacodynamic biomarker for RNA therapeutics. 13/15

Exploring applications in non-malignant disease, we analyzed #cfRNA from patients with pulmonary conditions including COPD, COVID-19, and ARDS. Levels of normal lung cfRNA increased with severity of lung injury and were higher in active smokers than never/former smokers. 12/15

As proof-of-concept, we also explored multi-cancer detection and tissue-of-origin classification in liver, pancreatic, and prostate cancers. Sensitivity ranged from 80-100% across cancer types, and tissue-of-origin was correctly predicted in most patients. 11/15

A potential application of #cfRNA is detection of resistance mechanisms. For example, we show that small cell transformation, a resistance mechanism to #EGFR inhibitors, can be detected using RARE-Seq, something that is not possible using mutant #ctDNA analysis. 10/15

Combining expression and mutation features into a single machine learning classifier further improved lung cancer detection, with AUCs of 0.94-0.95 in our training and external validation cohorts. 9/15

We also developed a method to genotype directly from #cfRNA, focusing on actionable variants in NSCLC. 8/15

Using customized bioinformatics, we detected lung cancer with 73% sensitivity at 95% specificity. Sensitivity increased with stage, and RNA levels correlated with #ctDNA VAFs. Strikingly, RARE-Seq detected lung cancer in more samples than tumor-naïve ctDNA analysis. 7/15

RAG-focused RARE-Seq was applied to plasma from over 360 individuals with cancer or non-malignant conditions and controls. Compared to healthy controls, genes known to be expressed in #LungCancer were highly enriched in the blood of lung cancer patients. 6/15

We also show that targeting transcripts lowly expressed or absent from healthy control plasma (“rare abundance genes” [RAGs]) can improve the limit of detection by >50-fold. 5/15

Many aspects of our approach are key to maximizing sensitivity. For example, we found that platelets are major confounders of #cfRNA analyses and developed an approach to computationally remove this unwanted variation, which increased assay sensitivity. 4/15

In this study, we describe end-to-end optimization of RARE-Seq, including:.-Blood collection and storage.-Extraction & quantification of #cfRNA.-Library preparation & sequencing.-Customized bioinformatics analysis methods.3/15

This work was led by @monica_n52010, @luca_bogdan, and Young-Jun Jeon and co-supervised by @AshAlizadeh. It was made possible by great collaborations between @StanfordCancer, @MGHCancerCenter, @sloan_kettering, and others. Many thanks to all involved! 2/15.

Excited to share our study describing a new liquid biopsy method called RARE-Seq for analyzing cell-free RNA (#cfRNA) that is out today in @Nature. 1/15

NCCN Guidelines for DLBCL now include ctDNA MRD testing. This is a major advance for patients and the liquid biopsy field. Congrats to the Foresight Diagnostics team for this significant achievement!.

RT @UTSW_RadOnc: Thank you to @max_diehn for an insightful talk today on liquid biopsies for cancer detection and characterization. Our med….